Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial.

AIMS: We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer. MATERIALS AND METHODS: This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin-5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%. RESULTS: Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases. CONCLUSION: FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.

Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients.

Cardiac resynchronization therapy is not effective in a variable proportion of heart failure patients. An accurate knowledge of each patient's electroanatomical features could be helpful to determine the most appropriate treatment. The goal of this study was to analyze and quantify the sensitivity of left ventricular (LV) activation and the electrocardiogram (ECG) to changes in 39 parameters used to tune realistic anatomical-electrophysiological models of the heart. Electrical activity in the ventricles was simulated using a reaction-diffusion equation. To simulate cellular electrophysiology, the Ten Tusscher-Panfilov 2006 model was used. Intracardiac electrograms and 12-lead ECGs were computed by solving the bidomain equation. Parameters showing the highest sensitivity values were similar in the six patients studied. QRS complex and LV activation times were modulated by the sodium current, the cell surface-to-volume ratio in the LV, and tissue conductivities. The T-wave was modulated by the calcium and rectifier-potassium currents, and the cell surface-to-volume ratio in both ventricles. We conclude that homogeneous changes in ionic currents entail similar effects in all ECG leads, whereas the effects of changes in tissue properties show larger inter-lead variability. The effects of parameter variations are highly consistent between patients and most of the model tuning could be performed with only ~10 parameters.

A modified sentinel lymph node technique combined with endoluminal loco-regional resection for the treatment of rectal tumours: a 14-year experience.

AIM: After endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgey (TEM) the N parameter may remain undefined. Nucleotide-guided mesorectal excision (NGME) improves the lymph node harvest. The aim of the present study is to evaluate the long-term oncological results after ELRR with NGME. METHOD: A total of 57 patients were enrolled over the period January 2001 to June 2015. All patients underwent ELRR by TEM. Prior to surgery, 99 m-technetium-marked nanocolloid was injected into the peritumoural submucosa. After removal of the specimen, the residual defect was probed to detect any residual radioactivity and 'hot' mesorectal fat was excised. All patients were included in a 5-year follow-up programme. RESULTS: Significant radioactivity in the residual cavity was found in 28 out of 57 patients (49%). The mean number of lymph nodes harvest in irradiated and nonirradiated patients was 1.66 and 2.76, respectively. After 68.2 months' follow-up overall survival was 91.2%, disease-related mortality 3.5% and disease-free survival 89.5%. Two patients developed pulmonary metastases: one ypT3N0 patient underwent lung lobectomy after chemotherapy and one pT2N0 patient was managed with lung radiotherapy. Both patients are currently alive and disease-free at 48 months' follow-up. Two patients developed local recurrence 1 year after ELRR, both treated with neoadjuvant chemo-radiotherapy and total mesorectal excision. Comparing the present series with previous patients who did not undergo NGME, an increased number of harvested lymph nodes were observed, with a statistically significant difference (P = 0.0085). CONCLUSION: NGME during ELRR improves the lymph node harvest and staging accuracy. The long-term results showed satisfactory local (3.5%) and distant (7%) recurrence rates.

Anal function after endoluminal locoregional resection by transanal endoscopic microsurgery and radiotherapy for rectal cancer.

AIM: In patients with rectal cancer, surgery and chemoradiotherapy may affect anal sphincter function. Few studies have evaluated anorectal function after neoadjuvant chemoradiotherapy (n-CRT) and/or transanal endoscopic microsurgery (TEM). The aim of this study was to evaluate the effects of n-CRT and TEM on anorectal function. METHOD: Thirty-seven patients with rectal cancer underwent anorectal manometry and Wexner scoring for faecal incontinence at baseline, after n-CRT (cT2-T3N0 cancer) and at 4 and 12 months after surgery. Water-perfused manometry measured anal tone at rest and during squeezing, rectal sensitivity and compliance. Twenty-seven and 10 patients, respectively, underwent TEM without (Group A) or with n-CRT (Group B). RESULTS: In Group A, anal resting pressure decreased from 68 ± 23 to 54 ± 26 mmHg at 4 months (P = 0.04) and improved 12 months after surgery (60 ± 30 mmHg). The Wexner score showed a significant increase in gas incontinence (59%), soiling (44%) and urgency (37%) rates at 4 months, followed by clinical improvement at 1 year (41%, 26% and 18%, respectively). In group B, anal resting pressure decreased from 65 ± 23 to 50 ± 18 mmHg at 4 months but remained stable at 12 months (44 ± 11 mmHg, P = 0.02 vs preoperative values - no significant difference compared with evaluation at 4 months). Gas incontinence, soiling and urgency were observed in 50%, 50%, 25% and in 38%, 12% and 12% of cases, respectively, 4 and 12 months after treatment. CONCLUSION: TEM does not significantly affect anal function. Instead, n-CRT does affect anal function but without causing major anal incontinence.

Aberrant expression of the neuronal-specific protein DCDC2 promotes malignant phenotypes and is associated with prostate cancer progression.

By integrating gene profiling and immunohistochemical data with functional experiments in cell lines in this study we show for the first time that doublecortin (DCX) domain containing 2 (DCDC2), a protein belonging to the DCX family and involved in neuronal cell migration, is aberrantly expressed in prostate tumors whereas absent in normal prostate. Furthermore, in patients treated with radical prostatectomy, high levels of DCDC2 RNA were significantly associated with increased biochemical relapse (LogRank Mantel-Cox=0.012). Mechanistically, we found that the ETS transcription factor ESE3/EHF, which is expressed in normal prostate and frequently lost in prostate tumors, maintained DCDC2 repressed by binding to a novel identified ETS binding site in the gene promoter. Consistently, in prostate tumors and in cellular models of gain and loss of ESE3/EHF, the expression of DCDC2 and ESE3/EHF were inversely correlated. In prostate cancer cells, DCDC2 colocalized with microtubules and promoted cell migration and resistance to the microtubule-targeting drug taxol. Collectively, this study establishes DCDC2 as a novel ESE3/EHF oncogenic target in prostate cancer. These findings may be relevant for the clinical management of prostate cancer as DCDC2 may signal tumors more prone to relapse and resistant to taxol treatment.

A nationwide audit of the use of radiotherapy for rectal cancer in Italy.

BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.

Thirteen years' experience with laparoscopic transcystic common bile duct exploration for stones. Effectiveness and long-term results.

BACKGROUND: The aim of the present study was to evaluate the effectiveness and long-term results of laparoscopic transcystic common bile duct exploration (TC-CBDE). METHODS: Ductal stones were present in 344 of 3212 patients (10.7%) who underwent laparoscopic cholecystectomy (LC). The procedure was completed laparoscopically in 329 patients (95.6%), with TC-CBDE performed in 191 patients (58.1%) who are the object of this study, or with a transverse choledochotomy in 138 cases (41.9%). RESULTS: Biliary drainage was employed in 71 of 191 cases (37.2%). Major complications occurred in 10 patients (5.1%), including retained stones in 6 (3.1%). Mortality was nil. No patients were lost to follow-up (median: 118.0 months; range: 17.6-168 months). No signs of bile stasis, no recurrent ductal stones and no biliary stricture were observed. At present 182 patients are alive with no biliary symptoms; 9 have died from unrelated causes. CONCLUSIONS: Long-term follow-up after laparoscopic TC-CBDE proved its effectiveness and safety for single-stage management of gallstones and common bile duct stones.

Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period.

BACKGROUND: This study aimed to compare the results and the oncologic outcomes of transanal endoscopic microsurgery (TEM) with neoadjuvant radiochemotherapy and laparoscopic resection (LR), also with neoadjuvant radiochemotherapy, in the treatment of T(2)-N(0) low rectal cancer. METHODS: The study enrolled 40 patients with T2-N(0) rectal cancer, randomizing 20 to TEM (arm A) and 20 to LR (arm B). RESULTS: After neoadjuvant radiochemotherapy, tumor downstaging was observed for 13 patients (65%) in arm A (7 pT0 and 6 pT1) and in 11 patients (55%) in arm B (7 pT0 and 4 pT1). More than a 50% reduction of the tumor diameter was observed in four arm A cases and in six arm B cases. At a median follow-up period of 56 months (range, 44-67 months) in both arms, one local failure (5%) occurred after 6 months in arm A and one (5%) after 48 months in arm B. Distant metastases occurred in one arm A patient (5%) after 26 months of follow-up evaluation and in one arm B patient (5%) at 31 months. The probability of local or distant failure was 10% for TEM and 12% for laparoscopic resection, whereas the probability of survival was 95% for TEM and 83% for laparoscopic resection. CONCLUSIONS: The findings show comparative results between the two study arms in terms of probability of failure and survival.

Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fields.

Human peripheral blood leukocytes from healthy volunteers have been employed to investigate the induction of genotoxic effects following 2 h exposure to 900 MHz radiofrequency radiation. The GSM signal has been studied at specific absorption rates (SAR) of 0.3 and 1 W/kg. The exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and temperature. The same temperature conditions (37.0 +/- 0.1 degrees C) were realized in a second waveguide, employed to perform sham exposures. The induction of DNA damage was evaluated in leukocytes by applying the alkaline single cell gel electrophoresis (SCGE)/comet assay, while structural chromosome aberrations and sister chromatid exchanges were evaluated in lymphocytes stimulated with phytohemagglutinin. Alterations in kinetics of cell proliferation were determined by calculating the mitotic index. Positive controls were also provided by using methyl methanesulfonate (MMS) for comet assay and mitomycin-C (MMC), for chromosome aberration, or sister chromatid exchange tests. No statistically significant differences were detected in exposed samples in comparison with sham exposed ones for all the parameters investigated. On the contrary, the positive controls gave a statistically significant increase in DNA damage in all cases, as expected. Thus the results obtained in our experimental conditions do not support the hypothesis that 900 MHz radiofrequency field exposure induces DNA damage in human peripheral blood leukocytes in this range of SAR.

Long-term results after laparoscopic transverse choledochotomy for common bile duct stones.

BACKGROUND: The aim of this study was to evaluate the long-term results of laparoscopic transverse choledochotomy (TC) during laparoscopic cholecystectomy (LC). METHODS: Ductal stones were present in 344 of 3,212 patients (10.7%) who underwent LC. The procedure was completed laparoscopically in 329 cases (95.6%), with a TC in 138 cases (41.9%) (the subjects of this study), and with a transcystic duct approach in 191 cases (58.1%). RESULTS: Biliary drainage was used in 131 of 138 cases (94.9%). There were major complications in eight patients (5.7%), and one patient died (0.7%). Retained stones were seen in 11 cases (8%). None of the patients was lost to follow-up (mean, 72.3 months; range, 11-145). Ductal stones recurred in five patients (3.6%). No signs of bile stasis and no biliary strictures were observed. In all, 121 patients are alive with no biliary symptoms; 16 have died from unrelated causes. CONCLUSION: Long-term follow-up after laparoscopic TC during LC proved its safety and efficacy.

Practice of opportunistic prostate-specific antigen screening in Italy: data from the Health Search database.

The effectiveness of prostate-specific antigen (PSA) testing for opportunistic screening of prostate cancer is not yet well established, although this practice seems to be widely accepted. To estimate the opportunistic use of PSA by general practitioners (GPs) in Italy, we conducted a survey by querying the Health Search (HS) database, which collects clinical records from a representative sample of the Italian population. Clinical computerized data from 320 GPs and 221,557 male patients were analysed. Among total requests for PSA, 3% were linked to prostate cancer, 18% to a urological disease or symptom and 79% were not linked to any urological condition (opportunistic screening). Opportunistic screening was used for 31.4% of subjects over 50 with a significant (P<0.0001) difference between geographical areas (36.4% north, 33.5% central regions, 22.9% south and isles). This distribution was very similar to prostate cancer prevalence as it resulted from the HS data. PSA testing practice showed an increase over the years (12.7% of men over 50 in 2000, 14.3% in 2001 and 15.9% in 2002). In conclusion, the practice of opportunistic screening of prostate cancer seems to be extensively adopted by Italian GPs and is becoming more and more popular, although to date it is not supported by strong scientific evidence.

Laparoscopic versus open hemicolectomy.

AIM: In the last decade, laparoscopic procedures are applied to the treatment of almost all colonic diseases, including both benign and malignant lesions. Focusing our attention to the laparoscopic operative technique, we compare the perioperative results and the oncological outcomes of laparoscopic hemicolectomy with those after open conventional hemicolectomy. METHODS: This prospective non randomized study is based on a series of 469 consecutive patients (73.6% with malignant lesions) operated on by the same surgical team following the same type of surgical technique, for laparoscopic and open approach, to perform right (RH) and left (LH) hemicolectomy, respectively, excluding segmental resections, emergency operations as well as transverse colon, splenic flexure and recurrent carcinomas. The treatment modality was selected by the patients after reading the informed consent form. Conversion rate to open surgery (for the laparoscopic group) and causes were assessed. Statistical significance (p) for operative time, resumption of gastrointestinal functions, length of stay, complications, perioperative mortality, as well as length of specimen, number of lymph-nodes harvest, incidence of local recurrences and distant metastases, and survival probability analysis in malignant cases, was assessed between the 2 groups (laparoscopic and open). RESULTS: From March 1992 to February 2003, 166 patients underwent RH and 303 LH. In the RH group, 108 patients underwent laparoscopic approach and 58 underwent open surgery (26 vs 13 for benign lesions and 82 vs 45 for adenocarcinomas, respectively). LH was performed by laparoscopy in 202 patients and by laparotomy in 101 (55 vs 30 for benign lesions and 147 vs 71 for adenocarcinomas, respectively). There were no conversions to open surgery in laparoscopic RH, while 10 patients (4.9%) in the laparoscopic LH group required conversion: 3 of 34 performed for diverticular disease and 7 of 147 performed for malignancy. Mean operative time for laparoscopic surgery was longer than for open surgery (182 vs 140 min for RH and 222 vs 190 min for LH, respectively), but with increasing experience this decreased significantly. Mean hospital stay in patients who underwent laparoscopic procedures was significantly shorter both in RH and LH groups (9.2 vs 13.2 days and 9.9 vs 13.2 days, respectively). Similar major complication rates were observed between the 2 laparoscopic and open groups (1.8% vs 1.7% for RH and 4.1% vs 4.9% for LH, respectively). Follow-up time ranged between 12 and 109 months (mean, 57.3 months) in RH groups and between 12 and 111 months (mean, 57.5 months) in LH groups. The follow-up dropout was of only 3 patients after RH (in the laparoscopic group) and 5 after LH (3 in the laparoscopic group and 2 in the open group). The local recurrence rate was lower after laparoscopic surgery in both arms (7% vs 8.8% for RH and 3.3% vs 7% for LH, respectively), but the differences were not statistically significant. Two port site recurrences were observed in the laparoscopic groups, 1 after a Dukes D palliative RH and 1 after a Dukes C LH converted to open surgery (1.7% and 0.9%, respectively). Metachronous metastases rates were similar between the laparoscopic and open groups (20.9% vs 17.6% for RH and 4.4% vs 5.3% for LH, respectively). Cumulative survival probability (CSP) at 72 months after laparoscopic RH was 0.791 as compared to 0.765 after open surgery (p=0.326) and 0.956 after laparoscopic LH as compared to 0.877 after open surgery (p=0.115). CSP for Dukes stage A, B and C in the laparoscopic RH group was 0.875, 0.846, and 0.727 as compared to 0.9 (p=0.815), 0.889 (p=0.87), and 0.6 (p=0.183) after open surgery, respectively. CSP for Dukes stage A, B and C in the laparoscopic LH group was 0.1, 0.966, and 0.885 as compared to 0.1 (p=0.936), 0.944 (p=0.466), and 0.7 (p=0.072) after open surgery, respectively. CONCLUSION: These results suggest that laparoscopic hemicolectomy for both benign and malignant lesions can be performed safely. Oncological outcomes were comparable with those of open surgery.

Long-term results of laparoscopic versus open resections for rectal cancer for 124 unselected patients.

BACKGROUND: Controversy continues to surround laparoscopic rectal resection for malignancy. A longer follow-up period is required to evaluate the long-term efficacy of the procedure and its impact on survival. Furthermore, no data from ongoing randomized controlled trials are yet available. The aims of this study were to compare long-term outcomes for unselected patients undergoing either laparoscopic or open rectal resection for cancer. METHODS: A series of 124 unselected consecutive patients with rectal cancer, who underwent surgery by the same surgical team, have been included in this study. Patients with T1N0 tumors underwent local excision, and emergency cases were excluded from the study. Written consent was submitted by each patient, and inclusion in either group (laparoscopic or open) was left to the patient's choice. The laparoscopic approach was chosen by 81 patients, and 43 patients chose open surgery. All the patients underwent preoperative radiotherapy (5,040 cGy), performed in selected cases with chemotherapy (for patients younger than 70 years). The following parameters were compared between the two groups: length of the surgical specimen, clearance of the margins of the specimen, number of lymph nodes identified, local recurrence rate, incidence of distant metastases, and survival probability analysis. The mean follow-up period for both groups was 43.8 months (range, l-9 years). RESULTS: We performed 60 laparoscopic and 27 open anterior resections, as well as 21 laparoscopic and 16 open abdomino perineal resections, respectively. No mortality occurred in either group. The mean length of the resected specimens was 24.3 cm in the laparoscopic group and 23.8 cm in the open group ( p = 0.47). The mean tumor-free margin was 3.0 cm in the laparoscopic group and 2.8 cm in the open group ( p = 0.57), and the mean number of lymph nodes identified was 10.3 in the laparoscopic group and 9.8 in the open group ( p = 0.63). Of the 124 patients, 86 (52 laparoscopic and 34 open) were included in out study. We excluded patients who underwent a palliative resection (6 laparoscopic and 6 open patients) or conversion to open surgery ( n = 10) and patients who had undergone surgery in the past year ( n = 16). One laparoscopic patient was lost to follow-up evaluation, whereas three laparoscopic patients and one open patient died of causes not related to cancer. No wound recurrence was observed. The local recurrence rate after laparoscopic resection was 20.8%, as compared with 16.6% after open resection ( p = 0.687). Distant metastases occurred in 18.2% of the patients in the laparoscopic group, as compared with 21.2% in the open group ( p = 0.528). Cumulative survival probability was 0.709 after laparoscopic resection after LR and 0.606 after open resection ( p = 0.162), whereas for Dukes' stages A, B, and C in the laparoscopic group versus the open group, it was 0.875 vs 0.889 ( p = 0.392), 0.722 vs 0.584 ( p = 0.199), and 0.500 vs 0.417 ( p = 0.320), respectively. At this writing 20 laparoscopic patients (62.5%) and 20 open patients (60.6%) are disease free ( p = 0.623). CONCLUSIONS: Oncologic surgical principles were respected. Long-term outcome after laparoscopic resection of rectal cancer was comparable with that after conventional resection. We should wait to draw conclusive scientific statements until the completion of ongoing international randomized controlled trials.

[Evaluation of the bactericidal activity of a disinfectant containing sodium hypochlorite (Amiclor)]. / Valutazione dell'attività battericida di un disinfettante a base di ipoclorito di sodio (Amiclor).

We evaluated the stability and the bactericidal activity of a disinfectant containing sodium hypochlorite (Amiclor), which associates the buffer effect of the system sodium carbonate/sodium tetraborate to the stabilizing action of sodium chloride. The stability was determined evaluating the trend of the active chlorine title in various conservation conditions and comparing it with a product having only sodium chloride as stabilizing component. The bactericidal activity, instead, was evaluated by suspension and surface tests against Escherichia coli (ATCC 10536) and in relation to several variables, as product concentration, contact time, presence of interfering substances and water hardness. From the obtained data it is possible to affirm that Amiclor owns a greater stability as regards the traditional products stabilized only with sodium chloride. The activity tests have pointed out that the practical conditions affect the choice of the combination "product concentration/contact time" necessary to obtain an effective bactericidal activity. The activity of Amiclor is conditioned by the presence of proteins in the mixture or on the surface of reaction. This influence is not very clear in clean conditions while it considerably increases in dirty conditions. A decrease of bactericidal activity was observed when the product was diluted in hard water, mainly for contact times of 5 minutes or low product concentrations.

The incidence, natural history and associated outcomes of influenza-like illness and clinical influenza in Italy.

OBJECTIVES: This study investigated the epidemiology, natural history and resource use associated with influenza in the general population setting in Italy. METHODS: For a 3-month winter epidemic period, 202 GPs reported daily the number of visits performed for influenza-like illness (ILI), clinical influenza and any other cause. In addition, the first 10 cases of clinical influenza requiring a doctor's visit in each month of the 3-month period and for a total of 30 cases per GP were recorded carefully and followed-up, for evaluation of clinical evolution, associated outcomes and resource use. RESULTS: Almost 200 000 visits were performed by 202 GPs, ILI and clinical influenza accounting for 13.8 and 8.3% of all-cause visits, respectively. A total of 6057 cases of clinical influenza were also recorded and evaluated for associated outcomes and resource use. Twenty percent of the patients were at risk because they were elderly (>65 years) or presented with concomitant chronic conditions. Almost all the patients received at least one prescription for symptomatic drugs and 36% received a prescription for antibiotics. Thirty-five percent of patients had at least one complication from influenza, primarily upper and lower respiratory tract bacterial infections. At-risk patients had a significantly higher complication rate (odds ratio = 2.89) and required more instrumental exams and hospitalizations compared with the general population, accounting for most of the direct costs associated with clinical influenza. Patients with clinical influenza had an average of 5 days absence from work or school. CONCLUSIONS: Influenza is associated with significant morbidity in the general and at-risk population, a high degree of resource use in the at-risk population and substantial reduction or loss of productivity in the active working Italian population.

Carbon monoxide, cigarettes and family doctors.

AIMS AND BACKGROUND: General practitioners could play a key role in preventive programs against tobacco-related diseases. However, they seldom take action in the office even with minimal advice counselling. Such behaviour might reflect the lack of academic teaching and the lack of practice with motivational and dependence questionnaires, considered basic tools to help smokers to quit successfully. The study was aimed to investigate the awareness of a sample of Italian family doctors as regards tobacco epidemiology and smoking cessation strategies. METHODS: A total of 428 family doctors were administered a questionnaire with a set of questions on their personal smoking habits and on personal initiatives in the office towards smokers. Another set of questions regarded their knowledge on tobacco issues, with special attention to carbon monoxide, which is widely perceived as a very dangerous poison and works as a motivational tool on smokers and adolescents. Carbon monoxide measurement was carried out on all participants to obtain objective data on smoking and to show the feasibility of the test. RESULTS: The percentage of self-reported current smokers among general practitioners was 24%, with a high prevalence of ex-smokers (46%), and 29% of never smokers. Family doctors were more keen to counsel adolescents than adults about tobacco, and they were very interested in continuing medical education on the issue. The doctors who took part in our study showed a surprising limited knowledge of all the issues associated with smoking cessation and prevention such as epidemiology, cigarette characteristics, success rate of smoking cessation programs, Fagerström's tolerance questionnaire, safety of nicotine replacement therapy and the knowledge of carbon monoxide as a product of cigarette smoke. CONCLUSIONS: The scenario depicted by our survey underscores the necessity to improve the knowledge and performance of primary care physicians on tobacco-related issues in order to implement primary and secondary prevention in clinical practice.

Outcome predictors in anorectic patients after 6 months of multimodal treatment.

BACKGROUND: Anorexia nervosa is a severe disorder that often responds poorly to treatment. At this time, little is known about pretreatment predictors of response. METHODS: A sample of 42 restrictor type anorectics was tested at the assessment phase and after 180 days retested using the Temperament and Character Inventory and Eating Disorder Inventory 2 along with other clinical evaluation instruments. After 180 days of treatment with multimodal 'network' therapy, the patients were divided into two groups. The first group included patients who showed relevant clinical improvement; the second group included patients considered 'not yet responding'. Data collected from the not-yet-responding group were compared by the t test with the other group's data to evaluate prognostic indexes. RESULTS: Diagnosis of personality disorder, which afflicted about 50% of patients, seemed not to be a relevant prognostic factor. However, a lower novelty seeking was characteristic of the nonresponder group. Higher levels of asceticism and maturity fears also characterized the nonresponder group. CONCLUSION: Present data suggest some elements that could be useful to focus pharmacotherapy, psychotherapy and family counseling on the current psychopathology of each patient.

Different effects of microwave energy and conventional heat on the activity of a thermophilic beta-galactosidase from Bacillus acidocaldarius.

The effect of microwave (f = 10.4 GHz) irradiation on a thermostable enzyme was experimentally tested, showing that irreversible inactivation is obtained. Enzymatic solutions (500 microliters, with concentrations between 10-100 micrograms/ml) were exposed at 70 degrees C, at SAR levels of 1.1 and 1.7 W/g for 15, 30, 45, or 60 min, and their activity was compared to that of a sample heated in a water bath at the same temperature. The residual activity of the exposed samples depends on enzyme concentration, microwave power level, and exposure time; activity was reduced to 10% in 10 micrograms/ml solutions treated at 1.7 W/g for 60 min. Microwave effects disappeared at concentrations above 50 micrograms/ml. These results were not found following water bath heating at the same temperature and durations.

Outcomes following repair of quadriceps tendon ruptures.

OBJECTIVES: The purpose of this study was to examine critically the outcomes of patients sustaining a quadriceps tendon rupture and to compare outcomes in patients with bilateral simultaneous ruptures versus a unilateral rupture. DESIGN: Retrospective review. SETTING: Patients were treated at a Level I trauma center. PATIENTS/PARTICIPANTS: Fifty-one quadriceps tendon ruptures in thirty-nine patients were evaluated. A mean four-year follow-up (range 13 to 204 months) was available for forty-eight tendon ruptures. INTERVENTIONS: All patients except one were treated with operative repair of the quadriceps tendon rupture(s). MAIN OUTCOME MEASUREMENTS: Patients were assessed by physical examination, Lysholm and Tegner scores, a functional questionnaire, quadriceps isokinetic testing, and radiographs. RESULTS: A statistically greater number of patients in the bilateral simultaneous rupture group had a systemic illness associated with tendon rupture (p = 0.014). This result did not adversely affect outcome as compared with patients with unilateral ruptures. Mean range of motion was 123 degrees in injured knees. Eighty-four percent of working patients returned to their previous occupations. More than half the patients, however, in general the most active, could no longer participate in their preinjury recreational activities. Fifty-three percent of unilateral rupture patients had persistent quadriceps strength deficits (>20 percent) in the injured extremity. Both quadriceps and hamstring isokinetic testing correlated significantly with Lysholm and Tegner scores. CONCLUSIONS: Most patients with bilateral simultaneous and unilateral tendon repairs can expect a good range of motion and return to their previous occupation, but many have persistent weakness and difficulty returning to higher level sporting activities.

Non-thermal effects of microwaves on proteins: thermophilic enzymes as model system.

Two thermophilic and thermostable enzymes, isolated from Sulfolobus solfataricus, S-adenosylhomocysteine hydrolase and 5'-methylthioadenosine phosphorylase, were exposed to 10.4 GHz microwave radiation in order to discriminate between thermal and non-thermal microwave effects. The exposure causes a non-thermal, irreversible and time-dependent inactivation of both enzymes; the inactivation rate is related to the energy absorbed and is independent of the enzyme concentration. The influence of salts on enzyme inactivation has also been investigated. Conformational changes of S-adenosylhomocysteine hydrolase, detected by fluorescence and circular dichroism techniques, suggest that microwaves induce protein structural rearrangements not related to temperature.